Age-related macular degeneration (AMD) is the leading cause of irreversible severe central visual loss in the aged population. Approximately 10% of people between the ages of 66 and 74 years will have some clinical findings of AMD. Epidemiological data suggest that AMD has a significant genetic component. Current evidence supports the hypothesis that variation of genes involved in immune function, DNA repair and oxidative stress plays a role in age-related diseases. We initiated the project in early 2003 by recruiting advanced AMD patients and controls. The aim of this study is to compare the allelic frequencies of single nucleotide polymorphisms (SNPs) within candidate genes in cohorts with AMD to the frequency in normal control subjects without AMD followed by the functional study of these SNPs by in vitro or in vivo experiments. Through this approach, we hope to identify genetic risk factors that could have functional implications in order to better understand and treat AMD. In FY2003, we have accomplished the following in our research: 1. Recruitment of 50 new AMD cases (total number: 118), 80 age-matched controls (total number:195), and 20 blood donor controls (total number:194); 2. Completion of 5000 SNP typing of 18 SNPs; 3. Reported an association between CX3CR1 SNP and AMD, Begin functional study of SNPs in CX3CR1 and CCL2 using biochemical and chemotaxis assay; 4. Expression profiling of tissue and/or cells with different SNP genotypes. Through the work described above, we published a scientific finding that CX3CR1-280M is a risk factor to AMD pathogenesis.